Drugs in Development Database

The Drugs in Development Database provides information about ALS drugs in development by biotechnology and pharmaceutical companies. It covers drugs in preclinical testing, as well as those that are currently in clinical development or were in the past. In addition, it includes information about select drugs in development for other neurodegenerative or neuromuscular diseases with a mechanistic link to ALS.

We hope this will provide a valuable source of information, and a resource for researchers in academia and industry to identify opportunities to collaborate on translational research in ALS.

We will continue to update the database with additional information and references, and will be implementing an improved search function soon! Please let us know of companies or drugs that that we should add to the list at [email protected].

Click a column header to sort alphabetically by that column. Click a drug name to see details.

(Click title to open drug details in a new window.)Company: Iron Horse TherapeuticsLocation: US-CaliforniaWebsite:http://www.coipharma.com/portfolio/Drug Type: Small moleculeConditions: ALSMechanism Type: Axon regenerationMechanism: 123C4 may help facilitate the repair of damaged motor neuronal axons by blocking EphA4-mediated signaling. The drug, which acts as an EphA4 agonist, may remove EphA4 from motor neuron surfaces by receptor-mediated endocytosis.U.S. Status for ALS: PreclinicalCommercial Information: The drug is licensed from the University of California Riverside. It is based on a study from the laboratory of Maurizio Pellecchia.R&D Status: The drug is now being optimized and is at the preclinical stage.

(Click title to open drug details in a new window.)Company: ZZ BiotechLocation: US-TexasWebsite:http://www.zzbiotech.comDrug Type: Protein BiologicConditions: ALS, stroke, sepsisMechanism Type: NeuroprotectionMechanism: 3K3A-APC is a recombinant Activated Protein C (APC), a protease with anticoagulant and cytoprotective properties for the aging and damaged brain. The CNS-penetrant drug candidate is being developed for stroke and other neurodegenerative disorders. Preclinical studies in SOD1 ALS mouse models have shown that 3K3-APC treatment increases lifespan by 13% and disease duration by 28% compared to saline treated control. The drug is no longer being actively developed for ALS.U.S. Status for ALS: InactiveCommercial Information: The company was founded based on discoveries from the laboratory of Prof. Berislav Zlokovic, MD, PhD, of the Keck School of Medicine at University of Southern California, Los Angeles, CA. The last company update was in 2014.R&D Status: A Phase II study evaluated safety, tolerability and activity of ZZ Biotech’s 3K3A-APC when given after tissue plasminogen activator, or tPA, in patients who have experienced moderately severe ischemic stroke. The study was completed in 2017. There is currently no disclosed program ongoing in ALS.

(Click title to open drug details in a new window.)Company: ShireLocation: US-MassachusettsWebsite:http://www.shire.comDrug Type: Protein BiologicConditions: ALS, Duchenne muscular dystrophyMechanism Type: Improving muscle functionMechanism: ACE-031 is a monoclonal antibody that binds and inhibits myostatin. It acts as a decoy receptor for myostatin and other proteins that limit muscle growth. Myostatin blockage has been considered as a therapeutic approach for ALS by improving muscle size and strength.U.S. Status for ALS: DiscontinuedCommercial Information: The programs was conducted in collaboration with Acceleron Pharma and was terminated in 2013.R&D Status: In May 2013 the Shire and Acceleron Pharma terminated a Phase II trial of ACE-031 in subject with Duchenne muscular dystrophy based on preliminary safety data.

(Click title to open drug details in a new window.)Company: Amylyx PharmaceuticalsLocation: US-MassachusettsWebsite:http://www.amylyx.comDrug Type: Small MoleculeConditions: ALS, Alzheimer's disease, Parkinson's disease.Mechanism Type: NeuroprotectionMechanism: AMX0035 a proprietary combination of two drugs, TUDCA and sodium phenylbutyrate, that acts by reducing cell death and neuronal inflammation in response to oxidative insult.U.S. Status for ALS: Phase IICommercial Information: AMX0035 is a proprietary combination of two drugs that contains tauroursodeoxycholic acid and sodium phenylbutyrate.R&D Status: The phase II clinical trial launched in June 2017.

(Click title to open drug details in a new window.)Company: Anelixis TherapeuticsLocation: US - MassachusettsWebsite:http://www.anelixistherapeutics.com/Drug Type: Protein BiologicConditions: ALSMechanism Type: ImmunomodulationMechanism: The blocking antibody to CD40L is designed to modulate the immune response associated with disease progression in ALS.U.S. Status for ALS: Phase ICommercial Information: Anelixis Therapeutics is a virtual biotechnology company that is the for-profit subsidiary of ALSTDI. Anelixis has in-licensed the rights to develop the CD40L antibody as a novel candidate therapy for ALS.R&D Status: Phase I

(Click title to open drug details in a new window.)Company: Anavex Life Sciences Corp.Location: US - New YorkWebsite:http://www.anavex.com/index.htmlDrug Type: Small MoleculeConditions: ALS, Alzheimer's disease, Parkinson's disease and other neurodevelopmental disorders.Mechanism Type: Sigma-1 receptor (S1R) and Muscarinic receptor agonistMechanism: ANAVEX 2-73, is a sigma-1 and muscarinic receptor agonist. The sigma-1 receptors are chaperone proteins localized to the endoplasmic reticulum (ER) membrane associated with mitochondria (MAMs), and function by helping protect against ER and oxidative stress. The sigma-1 receptors have been implicated in several neurodegenerative diseases, including ALS.U.S. Status for ALS: PreclinicalR&D Status: Phase IIa clinical trials, alone and in combination with donepezil (Anavex-Plus), for Alzheimer's disease were completed in November 2016. It is in preclinical development for ALS.

(Click title to open drug details in a new window.)Company: OrphazymeLocation: DenmarkWebsite:http://www.orphazyme.comDrug Type: Small moleculeConditions: ALSMechanism Type: Proteostasis, Protein misfolding modulatorMechanism: Arimoclomol is a small molecule that increases expression of 70-kDa heat shock proteins (Hsp70) and Hsp90s, chaperone proteins that play a role in folding of newly translated proteins and refolding or clearance of misfolded proteins.U.S. Status for ALS: Phase IIICommercial Information: In May 2011, Orphazyme acquired CytRx's molecular chaperone technology including the drug candidate arimoclomol, which is in clinical development for ALS.R&D Status: A larger phase III clinical trial launched in August 2018. The study is ongoing.

(Click title to open drug details in a new window.)Company: KadimastemLocation: IsraelWebsite:http://www.kadimastem.com/drug-discovery/7/neural-diseasesDrug Type: Stem Cell TherapyConditions: ALS, diabetes mellitusMechanism Type: NeuroprotectionMechanism: AstroRx is an experimental cell-based therapy. The approach involves the delivery of human embryonic stem cell-derived astrocyte precursor cells by intrathecal transplantation. The introduction of functional astrocyte precursor cells has the potential to regulate glutamatergic signaling, which is impaired in ALS patients, and thereby reduce neurotoxicity. Transplantation of astrocytes derived from stem cells into mutant SOD1 rats increases survival.U.S. Status for ALS: Phase I/IIA (Israel)Commercial Information: In December 2016, Kadimastem announced that they will partner with Corestem to further evaluate their stem cell strategy, AstroRx, in the Asia-Pacific region including South Korea. Kadimastem was founded based on patented technologies developing in the laboratory of Prof. Michel Revel (developer of the multiple sclerosis blockbuster drug, Rebif, and Kadimastem's Chief scientific Officer).R&D Status: A phase I/IIA clinical trial launched in March 2018. The clinical study will be conducted at Hadassah Medical Center in Jerusalem, Israel under the supervision of the Israeli Ministry of Health, and according to the outline coordinated with the FDA.

(Click title to open drug details in a new window.)Company: Biohaven PhamaceuticalsWebsite:http://biohavenpharma.com/Drug Type: Small MoleculeConditions: ALS, Alzheimer's Disease, Ataxia, Anxiety disorders, Affective disorders, Dementia, Dystonia, Rett Syndrome, TinnitusMechanism Type: Glutamate Excitotoxicity BlockerMechanism: BHV-0223 is a new form of riluzole that is easier to swallow. The drug, like riluzole, aims to protect motor neurons from further damage by reducing glutamate release from axon terminals.U.S. Status for ALS: INDR&D Status: A bioequivalence study launched in November 2017.

(Click title to open drug details in a new window.)Company: Biohaven PharmaceuticalsLocation: US-ConnecticutWebsite:http://biohavenpharma.com/Drug Type: Protein BiologicConditions: Spinocerebellar AtaxiaMechanism Type: Glutamate Excitotoxicity BlockerMechanism: BHV-4157 is a glutamate modulator that aims to protect neurons by reducing glutamate excitotoxicity.U.S. Status for ALS: N/ACommercial Information: Biohaven acquired the worldwide intellectual property rights from ALS Biopharma to a portfolio of over 300 prodrugs hat are glutamate modulators including BHV-4157. ALS Biopharma is affiliated with the Pennsylvania Drug Discovery Institute (www.padrugdiscovery.org) at the Pennsylvania Biotechnology Center of Bucks County in Doylestown, PA (www.pabiotechbc.org). R&D Status: BHV-4157 is currently being evaluated at phase II/III as a potential treatment for Spinocerebellar Ataxia.

(Click title to open drug details in a new window.)Company: BiogenLocation: US-MassachusettsWebsite:http://www.biogen.comDrug Type: Gene TherapyConditions: ALSMechanism Type: SOD1-Lowering TherapyMechanism: IONIS-SOD1Rx is a generation 2.0 antisense drug specifically designed to inhibit production of mutant superoxide dismutase (SOD1). SOD1 mutations account for approximately 20% of familial ALS cases.U.S. Status for ALS: Phase ICommercial Information: This program is a collaboration between Biogen and IONIS Pharmaceuticals (formerly ISIS).R&D Status: A Phase I clinical trial is recruiting participants as of Feb 2016. The clinical trial aims to determine the safety, tolerability and pharmacokinetics of SOD1RX in people with ALS. The study also aims to evaluate CSF SOD1 levels as a marker of target engagement to facilitate the development of SOD1-reducing therapies (Winer et al., 2013). Study completion is expected in July 2018.

(Click title to open drug details in a new window.)Company: Tivorsan PharmaceuticalsLocation: US-Rhode IslandWebsite:http://www.tivorsan.comDrug Type: Protein BiologicConditions: ALS, Duchenne muscular dystrophy (DMD)Mechanism Type: NMJ stabilizationMechanism: Recombinant biglycan (TVN-102) aims to stabilize neuromuscular junctions by increasing MuSK activation. The approach is based on previous studies which found that biglycan stabilizes these synapses in part, by regulating the localization and levels of MuSK at motor nerve terminals (Amenta et al., 2012).U.S. Status for ALS: PreclinicalCommercial Information: Tivorsan's lead candidate, TVN-102, is based on preclinical studies from Brown University's Justin Fallon, Ph.D., scientific founder of Tivorsan which found that biglycan stabilizes neuromuscular junctions.R&D Status: Preclinical studies in a SOD1 mouse model of ALS is planned. A phase I clinical trial of TVN-102 in DMD is expected to launch in 2017.

(Click title to open drug details in a new window.)Company: Catabasis PharmaceuticalsLocation: US-MassachusettsWebsite:http://www.catabasispharma.comDrug Type: Small MoleculeConditions: ALS, Friedriech's ataxiaMechanism Type: AnitoxidantMechanism: CAT-4001, an activator of Nrf2 and an inhibitor of NF-κB, aims to protect neurons by reducing oxidative stress and inflammation. The drug candidate, initially developed for Friedrich's ataxia, is a CNS-penetrant linked conjugate of monomethyl fumarate and docosahexaenoic acid which can be enzymatically cleaved upon cellular uptake, enabling release of both small molecules simultaneously. Studies in cellular and animal models have shown that the conjugate is more effective than either compound alone.U.S. Status for ALS: PreclinicalR&D Status: Preclinical studies and IND-enabling studies are ongoing for ALS and Friedreich's ataxia.

(Click title to open drug details in a new window.)Company: HerantisLocation: FinlandWebsite:http://www.herantis.com/Drug Type: Protein BiologicConditions: ALS, Parkinson's diseaseMechanism Type: NeuroprotectionMechanism: Enhancing trophic support from neurotrophic factors is beneficial in ALS mouse models. In preliminary unpublished studies, a single dose of one of these substances, cerebral dopamine neurotrophic factor (CDNF), improved survival in ALS mouse models. In non-human primate studies, CDNF has shown neuroprotective and regenerative capacity for dopamine-generating cells. Signs of efficacy are also seen in non-motor symptoms based on preclinical studies.U.S. Status for ALS: PreclinicalCommercial Information: In 2016, Herantis received orphan drug designation for CDNF for ALS by both the European Medicines Agency and the US Food and Drug Administration. Clinical development, however, has yet to begin for ALS according to Herantis. The drug is currently being evaluated as a potential therapy for Parkinson's disease at the phase I/II stage.R&D Status: Preclinical

(Click title to open drug details in a new window.)Company: Roche PharmaceuticalsLocation: SwitzerlandWebsite:http://www.roche.comDrug Type: Small MoleculeConditions: ALS, Spinal Muscular AtrophyMechanism Type: Glutamate Excitotoxicity BlockerMechanism: Ceftriaxone is a cephalosporin antibiotic that protects neurons from glutamate excitotoxicity by increasing the expression of the astrocytic excitatory amino acid transporters (EAAT2, or Glt-1). U.S. Status for ALS: DiscontinuedR&D Status: Ceftriaxone is an FDA approved antibiotic. It was under development as a potential ALS therapy. However, in August 2012 the Phase III ALS clinical trial of the antibiotic ceftriaxone was discontinued due to lack of statistically significant effect on disease progression in ALS.

(Click title to open drug details in a new window.)Company: Teva Pharmaceutical IndustriesLocation: IsraelWebsite:http://www.tevapharm.comDrug Type: Protein BiologicConditions: ALSMechanism Type: ImmunomodulationMechanism: Copaxone is a synthetic protein composed of four amino acids found in myelin basic protein (MBP). The drug simulates MBP, and prevents damage to myelin caused by T-cells.U.S. Status for ALS: DiscontinuedR&D Status: A Phase II trial in ALS testing Copaxone injections in ALS patients was completed in 2009 and no impact on disease progression was observed. The program was discontinued. The drug is FDA approved for relapsing remitting multiple sclerosis.

(Click title to open drug details in a new window.)Company: ProCypra TherapeuticsLocation: US-CaliforniaWebsite:http://www.colmeddev.com/procypra/Drug Type: Small MoleculeConditions: ALS, Parkinson's diseaseMechanism Type: SOD1 MetalationMechanism: Cu(II)ATSM is a bisthiosemicarbazone which selectively delivers copper to cells with impaired mitochondrial electron transport chains, a characteristic of ALS and many other neurodegenerative diseases. In both SOD1 mouse models of ALS and in ALS patients, scientists have found alterations in copper homeostasis, providing a rationale for testing this candidate in ALS. In a series of publications in mouse models of ALS, Cu(II)ATSM improved motor function and prolonged survival.U.S. Status for ALS: Phase ICommercial Information: ProCypra is a subsidiary of Collaborative Medicinal Development (CMD). CMD licensed commercial rights to the Cu(II)ATSM technology from the University of Melbourne Australia. The company is founded based on work from Kevin Barnham, Paul Donnelly and Anthony White at the University of Melbourne, as well as Peter Crouch, who led the studies in ALS.R&D Status: A phase I trial of Cu(II)ATSM in ALS is currently recruiting in Australia. Radiolabeled Copper 64-ATSM is also in clinical testing in the U.S. as a hypoxia imaging agent at low doses.

(Click title to open drug details in a new window.)Company: M’s Science CorporationLocation: JapanWebsite:http://www.m-sci.com/e/Drug Type: Small MoleculeConditions: ALS, depression, strokeMechanism Type: Sigma-1 receptor (S1R) agonistMechanism: Cutamesine is a highly selective sigma-1 receptor (S1R) agonist, which is being developed for ALS. S1R mutations are associated with juvenile ALS, and mouse studies suggest S1R agonists may have therapeutic benefit in ALS.U.S. Status for ALS: N/AR&D Status: A Phase I clinical trial in ALS was completed in Japan and the EU. A Phase II trial was completed in stroke in Japan and the EU.

(Click title to open drug details in a new window.)Company: Denali TherapeuticsWebsite:http://www.denalitherapeutics.comDrug Type: Small MoleculeConditions: ALS, Alzheimer's DiseaseMechanism Type: Neuroprotection, Necroptosis BlockerMechanism: A RIPK1 kinase inhibitor. This drug aims to protect motor neurons by blocking necroptosis, which may destroy motor neurons in ALS.U.S. Status for ALS: PreclinicalCommercial Information: This drug is licensed from Harvard University. It is based on the work of Junying Yuan at Harvard Medical School.R&D Status: A phase I clinical trial of healthy volunteers is planned in Europe.

(Click title to open drug details in a new window.)Company: BiogenLocation: US-MassachusettsWebsite:http://www.biogen.comDrug Type: Small MoleculeConditions: ALS, multiple sclerosis, Alzheimer's disease, spinal muscular atrophyMechanism Type: Mitochondrial bioenergeticsMechanism: The compound is a small molecule modulator of mitochondrial bioenergetics.U.S. Status for ALS: DiscontinuedCommercial Information: Following positive outcomes in a Phase II clinical trial in ALS sponsored by Knopp Biosciences, the compound was licensed to Biogen-Idec (now Biogen) from Knopp Biosciences. The Phase III clinical trial was sponsored by Knopp in collaboration with Biogen, but the drug did not show efficacy on any of the outcome measures examined.R&D Status: Discontinued by Biogen. A Phase III trial of dexpramipexole that enrolled 943 patients was completed in 2012, and the compound did not show efficacy on any of the endpoints assessed. The primary outcome measure assessed was a joint rank analysis of both survival and function. The Phase III extension study in collaboration with Biogen was terminated based on these results. Knopp is still developing the drug for other indications including hypereosinophilic syndromes.

(Click title to open drug details in a new window.)Company: Eisai Company, Ltd.Location: JapanWebsite:http://www.eisai.comDrug Type: Small MoleculeConditions: ALSMechanism Type: NeuroprotectionMechanism: E0302 (mecobalamin) is a coenzyme form of vitamin B(12), and acts as an important cofactor in the activities of B(12)-dependent methyltransferases. It is approve and marketed as a treatment for peripheral neuropathies in Japan. The mechanism of action in unknown, but some studies suggest that it is neuroprotective and leads to axonal regeneration.U.S. Status for ALS: N/AR&D Status: A Phase II/III clinical trial of ultra high dose of mecobalamin (E0302) in ALS was completed in July 2014, and a long term study is ongoing. In May 2015, Eisai submitted a new drug application for E0302 for ALS in Japan, but the NDA was withdrawn in March 2016 following a meeting with the Japanese regulatory agency, the Pharmaceuticals and Medical Devices Agency (PMDA), due to insufficient evidence for approval. The drug is approved and marketed in Japan for peripheral neuropathies and other conditions. In the United States, mecobalamin can be purchased over the counter at formulations of lower doses (up to 2500 microgram, while it is being tested at 25 mg and 50mg doses) but clinical testing for ALS is not ongoing.

(Click title to open drug details in a new window.)Company: Mitsubishi Tanabe Pharma CorporationLocation: JapanWebsite:http://www.mt-pharma.co.jpDrug Type: Small MoleculeConditions: ALS, strokeMechanism Type: AnitoxidantMechanism: Edaravone is a free radical scavenger, which functions as an antioxidant by neutralizing peroxyl radicals and peroxynitrite. In mouse models of ALS, edaravone reduced motor neuron loss and functional decline. The drug is thought to help protect motor neurons in ALS by reducing oxidative stress.U.S. Status for ALS: FDA ApprovedR&D Status: Edaravone is approved for the treatment of ALS in the US, Japan and South Korea.

(Click title to open drug details in a new window.)Company: Stealth BioTherapeuticsLocation: US-MassachusettsWebsite:http://www.stealthbt.com/Drug Type: Small MoleculeConditions: Barth syndrome, Mitochondrial myopathiesMechanism Type: Mitochondrial bioenergeticsMechanism: Elamipretide targets cardiolipin, a lipid residing in the mitochondrial inner membrane, which is critical to maintaining mitochondrial function and cellular energy supply. Elamipretide, formerly known as Bendavia, has been shown to promote energy production and reduce the production of excess of reactive oxygen species. This drug could have potential applications in neurodegenerative diseases, including ALS.U.S. Status for ALS: PreclinicalR&D Status: Clinical trials for several conditions are ongoing. The approach is currently being evaluated at phase 3, as a potential treatment for mitochondrial myopathies.

(Click title to open drug details in a new window.)Company: Forum Pharmaceuticals (formerly EnVivo Pharmaceuticals)Location: US-MassachusettsWebsite:http://www.forumpharma.comDrug Type: Small MoleculeConditions: FTDMechanism Type: Epigenetics, HDAC inhibitorMechanism: FRM-0334 is a brain penetrant histone deacetylase (HDAC) inhibitor which is being developed as a therapy for frontotemporal dementia (FTD) due to progranulin haploinsufficiency. FRM-0334 has been shown to increase progranulin expression in rodents and in cells derived from patients carrying granulin mutations.U.S. Status for ALS: N/ACommercial Information: The company closed in the summer of 2016. The status of this drug candidate is unknown.R&D Status: Forum Pharma initiated a Phase II trial in FTD. As of May 2015, the study was recruiting participants.

(Click title to open drug details in a new window.)Company: ALS Therapy Development InstituteLocation: US-MassachusettsWebsite:http://www.als.netDrug Type: Small moleculeConditions: ALSMechanism Type: ImmunomodulationMechanism: TDI-132 (aka: fingolimod/ Novartis' drug Gilenya) is an agonist of the sphigosine 1 phosphate receptor.It blocks T-cell infiltration into the CNS by reducing their circulation in the blood and retaining them in the lymph nodes. The drug is being developed to reduce neuroinflammation associated with disease progression in ALS.U.S. Status for ALS: InactiveCommercial Information: For full details of the ALS TDI pipeline click here: http://www.alstdi.org/als-research/.R&D Status: Gilenya is approved for treating relapsin-remitting forms of multiple sclerosis.

(Click title to open drug details in a new window.)Company: GenentechLocation: US-CaliforniaWebsite:http://www.gene.comDrug Type: UnknownConditions: ALSMechanism Type: Glutamate Excitotoxicity BlockerMechanism: GDC-0134 is an inhibitor of the dual leucine zipper kinase (DLK). It aims to promote survival of motor neurons in ALS by reducing glutamate-mediated excitotoxicity. U.S. Status for ALS: Phase ICommercial Information: This approach is being developed by Genentech. In 2017, researchers at Genentech reported that DLK is upregulated in patients and may contribute to neurodegeneration in the disease.R&D Status: A Phase I clinical trial trial of safety and pharmacokinetics of GDC-0134 in ALS opened in 2016.

(Click title to open drug details in a new window.)Company: Genervon BiopharmaceuticalsLocation: US-CaliforniaWebsite:http://www.genervon.com/Drug Type: Protein BiologicConditions: ALS, stroke, Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple sclerosisMechanism Type: NeuroprotectionMechanism: GM604 is based on motorneuronotrophic factor (MNTF), a fetally expressed six amino acid endogenous neurotrophin that exhibits neuroprotective, anti-apoptotic, anti-oxidative and anti-inflammatory effects. It acts according to Genervon by modulating 8 or more key pathways that are disrupted in ALS. U.S. Status for ALS: Phase IIACommercial Information: GM604 was the subject of a large campaign from the ALS patient and caregiver community to accelerate approval of this therapy for ALS, but many scientists in the ALS research community expressed the need for further validation of the results in larger patient cohorts over longer periods of time.R&D Status: The drug was granted Orphan Drug and Fast Track Designation by the U.S. FDA. A Phase IIA clinical trial in ALS that enrolled 12 patients was completed in 2014. Results from a Phase IIA trial in 12 patients suggest that GM604 is well tolerated. A larger Phase III study based on a longer treatment period is now being planned according to Genervon.

(Click title to open drug details in a new window.)Company: CongeniaLocation: ItalyWebsite:http://www.congenia.it/Drug Type: Small MoleculeConditions: ALSMechanism Type: Mitochondrial protectantMechanism: Gnx4728 is an inhibitor of the mitochondrial Permeability Transition Pore (mPTP). Increases in mitochondrial permeability are associated with mitochondrial swelling and rupturing, calcium release and release of apoptotic factors. Congenia is collaborating with academic researchers on testing their proprietary inhibitor Gnx4728 in mouse models of ALS.U.S. Status for ALS: PreclinicalCommercial Information: Congenia is a biotechnology company owned by Genextra.R&D Status: Preclinical

(Click title to open drug details in a new window.)Company: ImStar TherapeuticsLocation: CanadaWebsite:http://www.imstartx.com/Drug Type: Small MoleculeConditions: ALSMechanism Type: Proteostasis, Protein misfolding modulatorMechanism: IMS-088 is a novel compound derived from withaferin A, a natural compound isolated from the leaves of the winter cherry plant, with improved pharmacological properties for a therapeutic drug. Studies in the SOD1 mouse model of ALS have shown that presymptomatic treatment with withaferin A prolongs survival in this model and reduces misfolded SOD1 levels. A subsequent analysis suggests this reduction may be due to, upon treatment, an increase in heat shock protein 25 (a mouse ortholog of heat shock protein 27).U.S. Status for ALS: PreclinicalCommercial Information: The company was co-founded by Dr. Jean-Pierre Julien from Laval University. The last update from the company was in January 2014.R&D Status: Preclinical

(Click title to open drug details in a new window.)Company: Immunity PharmaLocation: IsraelWebsite:http://www.immunitypharma.com/Drug Type: Protein BiologicConditions: ALSMechanism Type: NeuroprotectionMechanism: IPL344 is an activator of the Akt pathway, a key signaling pathway in cell survival and repair.In mutant SOD1 mouse models of ALS, IPL344 delayed disease progression and prolonged survival.U.S. Status for ALS: PreclinicalCommercial Information: Immunity Pharma's drug candidates were originally discovered laboratory of Prof. Irun R. Cohen at the Weizmann Institute of Science in Rehovot, Israel. The last update from the company was in 2012, and it is unclear whether this program is active.R&D Status: Preclinical

(Click title to open drug details in a new window.)Company: MediciNovaLocation: US-CaliforniaWebsite:http://www.medicinova.comDrug Type: Small MoleculeConditions: ALS, multiple sclerosis, neuropathic pain, addictionMechanism Type: ImmunomodulationMechanism: Ibudilast is an orally bioavailable, centrally acting phosphodiesterase inhibitor that attenuates glial cell activation, at least in part, by reducing the effect of proinflammatory factors. MN-166 may minimize the production of pro-inflammatory cytokines.U.S. Status for ALS: Phase IIR&D Status: In 2014, MedicinNova received FDA approval to begin a Phase II trial of MN-166 in ALS. In 2015, the FDA approved a new clinical protocol to add on a biomarker study component using a novel imaging technology, and to assess the effect of MN-166 on this biomarker. The study was completed at the end of 2017.

(Click title to open drug details in a new window.)Company: Karyopharm TherapeuticsLocation: US-MassachusettsWebsite:https://www.karyopharm.com/sine-technology/Drug Type: Small MoleculeConditions: ALSMechanism Type: Nuclear Export BlockerMechanism: This approach, which targets exportin 1 (XPO1), aims to protect motor neurons in ALS by blocking nuclear export. The strategy may reduce motor neuron toxicity in ALS in part, by helping keep TDP-43 from building up in the cytoplasm (see Chou et al., 2018).U.S. Status for ALS: PreclinicalCommercial Information: In January 2018, Biogen obtained the rights to further develop this approach as a potential therapy for neurological diseases including ALS.R&D Status: This drug candidate is being further developed as a potential therapy for ALS by Biogen in Cambridge, Massachusetts.

(Click title to open drug details in a new window.)Company: TauRx TherapeuticsLocation: SingaporeWebsite:http://www.taurx.comDrug Type: Small MoleculeConditions: Alzheimer's disease, bvFTDMechanism Type: Proteostasis, Aggregation BlockerMechanism: LMTX reduces levels of aggregated or misfolded Tau proteins according to preclinical studies. The active ingredient, methyltionininium, also targets aggregation of synuclein, TDP-43 and huntingtin.U.S. Status for ALS: PreclinicalR&D Status: LMTX is in being tested in Phase III trials for mild and moderate Alzheimer's disease and behavioral variant frontotemporal dementia. Phase I trials in Parkinson's disease are also ongoing.

(Click title to open drug details in a new window.)Company: M’s Science CorporationLocation: JapanWebsite:http://www.m-sci.com/e/Drug Type: Small MoleculeConditions: Parkinson's diseaseMechanism Type: Sigma-1 receptor (S1R) agonistMechanism: MC116 is a sigma-1 receptor (S1R) agonist, which is being developed for Parkinson's disease. This is a potentially interesting compound for ALS, since S1R mutations are associated with juvenile ALS, and mouse studies suggest S1R agonists may have therapeutic benefit in ALS.U.S. Status for ALS: N/AR&D Status: N/A

(Click title to open drug details in a new window.)Company: miRagen TherapeuticsLocation: US-ColoradoWebsite:http://www.miragentherapeutics.comDrug Type: Gene TherapyConditions: ALSMechanism Type: ImmunomodulationMechanism: MRG-107 is an oligonucleotide drug that targets miR-155, a microRNA that is elevated in the spinal cord of patients with ALS, and in ALS mouse models. It is emerging as a key player in neuroinflammation and immune regulation, and therefore is a therapeutic target of interest in ALS.U.S. Status for ALS: PreclinicalR&D Status: MRG-107 is at the stage of investigational new drug (IND)-enabling studies in ALS.

(Click title to open drug details in a new window.)Company: AB ScienceLocation: FranceWebsite:http://www.ab-science.com/Drug Type: Small MoleculeConditions: ALS, Alzheimer's disease, multiple sclerosis, stroke, cancer, rheumatoid arthritisMechanism Type: ImmunomodulationMechanism: Masitinib is thought to reduce inflammation in ALS by blocking microgliosis, at least in the spinal cord. (Trias et al., 2016). The drug may also help protect peripheral motor neurons in ALS by inhibiting the infiltration of macrophages and mast cells. Masitinib is an enzymatic inhibitor which blocks tyrosine kinases including CSF1R, c-Kit and PDGFRα/β.U.S. Status for ALS: Phase IIICommercial Information: France discontinued evaluation of this drug as a potential therapy for non-fatal conditions in 2015 due to severe adverse side effects observed in clinical studies.R&D Status: A second Phase III clinical trial of masitinib in combination with riluzole is planned. Locations will include the U.S, Canada and Europe.

(Click title to open drug details in a new window.)Company: Oxford BiomedicaLocation: United KingdomWebsite:http://www.oxfordbiomedica.co.uk/Drug Type: Gene TherapyConditions: ALSMechanism Type: NeuroprotectionMechanism: MoNuDin is a lentiviral vector technology for delivering vascular endothelial growth factor (VEGF) to motor neurons for the treatment of ALSU.S. Status for ALS: InactiveCommercial Information: The program is being conducted in collaboration with VIB/University of Leuven and is being funded by the UK Motor Neurone Disease AssociationR&D Status: According to the Oxford BioMedica website, the preclinical studies were expected to be completed by the end of 2016. The MoNuDin webpage on Oxford BioMedica's website has since been removed.

(Click title to open drug details in a new window.)Company: N/ALocation: US-New YorkDrug Type: Protein BiologicConditions: ALSMechanism Type: NMJ stabilizationMechanism: This antibody-based approach aims to help muscle fibers and motor neurons stay connected in ALS by increasing the activity of the muscle-specific tyrosine kinase MuSK, a key enzyme that stabilizes neuromuscular junctions.U.S. Status for ALS: PreclinicalCommercial Information: The approach, originally developed by Genentech, is being further developed by Steve Burden and colleagues at New York University School of Medicine.

(Click title to open drug details in a new window.)Company: Neurimmune TherapeuticsLocation: SwitzerlandWebsite:http://www.neurimmune.comDrug Type: Protein BiologicConditions: ALS, frontotemporal dementia, Alzheimer's diseaseMechanism Type: Protein aggregate clearance, TDP-43 Mechanism: NI-205 is a human-derived monoclonal antibody that targets TDP-43. Pathological cytoplasmic aggregates of TDP-43 are a hallmark of ALS and ALS/frontotemporal dementia, and mutations in the gene are associated with both diseases.U.S. Status for ALS: PreclinicalCommercial Information: This asset is being developed in partnership with BIogen.R&D Status: Preclinical

(Click title to open drug details in a new window.)Company: Neurimmune TherapeuticsLocation: SwitzerlandWebsite:http://www.neurimmune.comDrug Type: Protein BiologicConditions: ALS, FTDMechanism Type: Not DisclosedMechanism: NI-308 is a human-derived monoclonal antibody that targets an undisclosed target for ALS/FTD.U.S. Status for ALS: PreclinicalR&D Status: Preclinical

(Click title to open drug details in a new window.)Company: Neuraltus PharmaceuticalsLocation: US-CaliforniaWebsite:http://www.neuraltus.comDrug Type: Small MoleculeConditions: ALS, Parkinson's disease, Alzheimer's disease, frontotemporal dementia, ataxis-telangiectasiaMechanism Type: ImmunomodulationMechanism: NP001 is a small molecule regulator of macrophage activation. It is thought to restore macrophages to their neuroprotective state and reduce inflammation seen in ALS. Treatment of ALS mouse models with NP001 extended survival. In the Phase IIa safety study, administration of a high dose of NP001 (2mg/kg) over a 6 month period was associated with a slowing of disease progression in 27% of patients, approximately 2.5 times greater than the percentage in patients on placebo (10%).U.S. Status for ALS: InactiveCommercial Information: The confirmatory Phase II study of NP001 in ALS is ongoing. It is being directed by Robert Miller, M.D., Director of the Forbes Norris MDA/ALS Research Center at California Pacific Medical Center in San Francisco, CA.R&D Status: A Phase II study was completed in 2012. A confirmatory Phase II study is ongoing. Neuraltus is establishing a managed access program for ALS patients in Europe.

(Click title to open drug details in a new window.)Company: Proclara BiosciencesLocation: US-MassachusettsWebsite:http://www.proclarabio.comDrug Type: Protein BiologicConditions: Alzheimer's disease, Parkinson's diseaseMechanism Type: Proteostasis, Protein misfolding modulatorMechanism: The company's technology revolved around the General Amyloid Interaction Motif (GAIM) technology that simultaneously targets multiple misfolded proteins or amyloids. The GAIM technology are able to both prevent the formation of new toxic protein aggregates and also clear existing aggregates in the form of both soluble oligomers and insoluble fibers, such as plaques and tangles. NPT088 is the GAIM motif fused to a portion of a human antibody, which can be easily administered to patients. This mechanism of action suggest that the GAIM technology could also be beneficial in ALS.U.S. Status for ALS: N/AR&D Status: Preclinical

(Click title to open drug details in a new window.)Company: NeuralStemLocation: US-MarylandWebsite:http://www.neuralstem.comDrug Type: Stem Cell TherapyConditions: ALS, spinal cord injuryMechanism Type: NeuroprotectionMechanism: NSI-566 are human spinal cord stem cell (HSSCs) that are administered into the gray matter of the spinal cord. In mouse models of ALS, NSI-566 cells expressed neutrophic factors and established synaptic connections with motor neurons. The cells are intended to provide neuroprotection to motor neurons in ALS patients.U.S. Status for ALS: Phase IIR&D Status: An open-label phase II clinical trial in ALS was completed in 2015. The trial found that stem cell transplantation was safe in people with ALS. The approach, however, did not slow progression of the disease according to a comparison to 3 historical control groups.

(Click title to open drug details in a new window.)Company: Neurotec PharmaLocation: SpainWebsite:http://www.neurotec-pharma.comDrug Type: Small MoleculeConditions: ALS, multiple sclerosis, strokeMechanism Type: ImmunomodulationMechanism: NT-K0-003 is a small molecule modulator of microglial activity that confers neuroprotection according to preclinical studies. The compound, also known as diazoxide, is a K-ATP potassium channel activator that may reduce inflammation by blocking microglial activation.U.S. Status for ALS: PreclinicalCommercial Information: A phase II clinical study of the drug demonstrated no significant benefit in relapsing-remitting multiple sclerosis (RRMS). The status of the drug is unknown.R&D Status: A Phase II study of NT-KO-001 for multiple sclerosis was completed in 2014.

(Click title to open drug details in a new window.)Company: MedipostLocation: South KoreaWebsite:http://www.medi-post.comDrug Type: Stem Cell TherapyConditions: ALS, Alzheimer's disease, strokeMechanism Type: NeuroprotectionMechanism: The Neurostem therapy consists of mesenchymal stem cells derived from allogeneic umbilical cord blood that are believed to confer therapeutic benefit by inducing the release of therapeutic proteins (i.e.: anti-apoptotic, anti-inflammatory and anti-oxidative stress) from endogenous cells through paracrine actions. The treatment is first being developed to treat Alzheimer's type dementia, but the company aims to also apply it to ALS and stroke.U.S. Status for ALS: N/AR&D Status: Medipost is currently conducting a Phase I/II trial of Neurostem for Alzheimer's disease in Korea.

(Click title to open drug details in a new window.)Company: N/ALocation: US-MarylandDrug Type: Gene TherapyConditions: ALS, Parkinson's diseaseMechanism Type: NeuroprotectionMechanism: The approach aims to help protect motor neurons in ALS in part, by stimulating axonal outgrowth and protecting against glutamate-induced excitotoxicity.U.S. Status for ALS: PreclinicalCommercial Information: The drug exhibited no significant benefit in Parkinson's disease according to a phase II clinical trial. But according to some studies, in at least some forms of PD, neurturin may be unable to promote survival of dopaminergic neurons and may be harder to deliver, particularly in advanced stages of the disease.R&D Status: This gene therapy is being developed as a potential therapy for ALS in the laboratory of Nicholas Maragakis at Johns Hopkins University School of Medicine in Baltimore, Maryland.

(Click title to open drug details in a new window.)Company: KineMedLocation: US-CaliforniaWebsite:http://www.kinemed.comDrug Type: Small MoleculeConditions: ALS, Parkinson's disease, diabetic neuropathyMechanism Type: Microtubule dynamics modulatorMechanism: Kinemed is developing noscapine and new analogues for neurodegenerative diseases and fibrotic diseases. Noscapine regulates abnormal microtubule (MT) dynamics, and reverses MT-mediated neuronal transport defects. The company has developed a proprietary technology for assessing MT turnover that is being developed as a biomarker in several neurodegenerative diseases, including ALS.U.S. Status for ALS: PreclinicalR&D Status: Preclinical

(Click title to open drug details in a new window.)Company: Anelixis TherapeuticsLocation: US - MassachusettsWebsite:http://www.anelixistherapeutics.com/Drug Type: Small MoleculeConditions: ALSMechanism Type: Proteostasis, Misfolded SOD1Mechanism: The company is aiming to identify small molecules that bind the misfolded SOD1 dimer and stabilize it, thereby preventing aggregation and seeding of protein misfolding in wild-type SOD1. Efforts are focused on medicinal chemistry followed by in vivo and in vitro optimization to identify compounds optimized for human testing.U.S. Status for ALS: PreclinicalCommercial Information: Anelixis Therapeutics is a virtual biotechnology company that is the for-profit subsidiary of ALSTDI.R&D Status: Preclinical

(Click title to open drug details in a new window.)Company: Aquinnah PharmaceuticalsLocation: US-MassachusettsWebsite:http://www.aquinnahpharma.com/Drug Type: Small MoleculeConditions: ALS, Alzheimer's diseaseMechanism Type: Stress granule clearanceMechanism: Aquinnah is developing compounds that eliminate TDP-43-positive stress granules which are estimated to persist in more than 75% of cases of the disease.U.S. Status for ALS: PreclinicalCommercial Information: The company screened more than 75,000 compounds to identify potential granules that eliminate TDP-43 positive stress granules. They are now developing an undisclosed subset of these compounds. The company is co-founded by Dr. Benjamin Wolozin from Boston University. R&D Status: Preclinical

(Click title to open drug details in a new window.)Company: Chaperone TherapeuticsLocation: US-North CarolinaWebsite:http://www.chaperonetherapeutics.comDrug Type: Small MoleculeConditions: ALS, Alzheimer's disease, Huntington's disease, Parkinson's Disease and other conditions.Mechanism Type: Proteostasis, Protein misfolding modulatorMechanism: Chaperone Therapeutics is developing small molecules that aim to activate HSF1, a key modulator of protein folding and stress response pathways. The approach aims to lower neuronal stress by reducing the buildup of misfolded proteins.U.S. Status for ALS: PreclinicalCommercial Information: In August 2015, Chaperone Therapeutics and ALS TDI announced a partnership to develop therapies for ALS.R&D Status: Preclinical

(Click title to open drug details in a new window.)Company: OptiKiraLocation: US-CaliforniaWebsite:http://www.optikira.comDrug Type: Small MoleculeConditions: ALS, diabetes, retinitis pigmentosaMechanism Type: Unfolded protein response (UPR), IRE1 alpha inhibitorMechanism: OptiKira is developing inhibitors of the unfolded protein response, specifically of inositol-requiring enzyme-1 alpha (IRE1α), a key activation step in the unfolded protein response (UPR). The technology has applications for ALS, although the company's current focus is diabetes and retinitis pigementosa.U.S. Status for ALS: PreclinicalCommercial Information: OptiKira was launched in 2015 by BioMotiv, the mission-driven accelerator associated with The Harrington Project for Discovery and Development. The technologies licensed by the company were developed in the laboratories of Scott Oakes and Feroz Papa at the University of California San Francisco and Bradley Backes (UCSF) and Dustin Maly (University of Washington).R&D Status: Preclinical

(Click title to open drug details in a new window.)Company: ProMIS NeurosciencesLocation: CanadaWebsite:http://www.promisneurosciences.com/Drug Type: Vaccine, Protein BiologicConditions: ALS, Alzheimer's diseaseMechanism Type: Misfolded SOD1 ClearanceMechanism: ProMIS is developing therapeutic approaches for immunization against disease-specific epitopes (DSE) of misfolded or aggregated mutant superoxide dismutase-1 (SOD-1). The company uses a dual approach of passive immunization with anti-SOD1 monoclonal antibodies, in combination with activate immunization with an anti-SOD1 vaccine to produce antibodies in the patient's body. The vaccine is expected to eliminate the misfolded protein, while sparing wild-type SOD-1.U.S. Status for ALS: PreclinicalCommercial Information: The company changed its name from Amorfix Life Sciences to ProMIS Neurosciences in July, 2015. The company is based around research from the laboratory of scientist Dr. Neil Cashman, Professor of Medicine at the University of British ColumbiaR&D Status: Preclinical

(Click title to open drug details in a new window.)Company: Verge GenomicsLocation: US-CaliforniaWebsite:http://www.vergegenomics.com/Drug Type:Conditions: ALS, Alzheimer's disease, Parkinson's diseaseMechanism Type: Computational analysisMechanism: Verge Genomics is applying network algorithms to large-scale gene expression data to map out clusters of co-regulated genes implicated in neurodegenerative diseases, including in ALS. They then examine publicly-available information to identify FDA-approved drugs that can be tested to affect the gene clusters of interest.U.S. Status for ALS: PreclinicalCommercial Information: The company was launched out of the YCombinator accelerator program by Alice Zhang and Jason Chen, both from the University of California, Los Angeles - Caltech MD/PhD program.R&D Status: Preclinical

(Click title to open drug details in a new window.)Company: Yumanity TherapeuticsLocation: US-MassachusettsWebsite:http://www.yumanity.comDrug Type: Small MoleculeConditions: ALS, Parkinson's disease, Alzheimer's diseaseMechanism Type: Proteostasis, Protein misfolding modulatorsMechanism: Yumanity’s innovative new approach to drug discovery and development concentrates on reversing the cellular phenotypes and disease pathologies caused by protein misfolding. Yumanity's discovery platform combines high-throughput screening in yeast cells with a human neural platform composed of induced pluripotent stem cells from patients, which allows for iterative and parallel analysis of results in both systems. In addition, the company has a drug-target identification platform that leverages yeast genetics and analysis of protein networks to identify drug targets. The company's lead candidate is for Parkinson's disease.U.S. Status for ALS: PreclinicalCommercial Information: Formed in 2014 by former CEO of Onyx Pharmaceuticals, Tony Coles, MD, and protein folding science pioneer, Prof. Susan Lindquist, PhD, from Massachusetts Institute of Technology in Cambridge, MA.R&D Status: Preclinical

(Click title to open drug details in a new window.)Company: miCure TherapeuticsLocation: IsraelWebsite:http://www.micurerx.comDrug Type: Gene TherapyConditions: ALSMechanism Type: MicroRNA therapeuticsMechanism: miCure Therapeutics is developing microRNA-based therapeutics for CNS disorders. The company is pursuing an approach to treat ALS by restoring microRNA expression to their endogenous levels.U.S. Status for ALS: PreclinicalCommercial Information: The company was founded based on technologies developed by Prof. Alon Chen and Dr. Eran Hornstein of the Weizmann Institute of Science in Rehovot, Israel.R&D Status: Preclinical

(Click title to open drug details in a new window.)Company: N/ALocation: GermanyDrug Type: Gene TherapyConditions: ALS, GlaucomaMechanism Type: Neuroprotection, Astrocyte-Mediated ToxicityMechanism: This gene therapy aims to reduce TGFß signaling via the delivery of an antisense oligonucleotide targeting TGFß receptor type-II (TGFßRII). The approach may be protect motor neurons in ALS, according to preclinical studies, in part, by reducing astrocyte-mediated toxicity.U.S. Status for ALS: PreclinicalCommercial Information: This gene therapy is being developed by the laboratory of Ulrich Bogdahn at the University of Regensburg in Germany. The approach is currently being evaluated in the clinic, in partnership with Isarna Therapeutics in Munich, Germany, at phase 1 as a treatment for an advanced form of glaucoma.

(Click title to open drug details in a new window.)Company: Avanir PharmaceuticalsLocation: US-CaliforniaWebsite:http://www.avanir.comDrug Type: Small MoleculeConditions: ALS, pseudobulbar affectMechanism Type: Sigma-1 receptor (S1R) and NMDA receptor agonistMechanism: Nuedexta is Avanir's first-in-class dual action drugs, which acts on both sigma-1 receptors and NMDA receptors. The precise mechanism of action is not known. Nuedexta diminishes the unpredictable emotional episodes of pseudobulbar affect (PBA) according to clinical studies (Schoedel et al., 2014). U.S. Status for ALS: FDA ApprovedCommercial Information: The active ingredient of Nuedexta is dextromethorphan. The drug is stabilized through a formulation which contains quinidine sulfate.R&D Status: The drug is FDA-approved for treating pseudobulbar affect (emotionality) which can occur in many neurological disorders including ALS and FTD. More recently, however, the drug has been shown to help some patients with ALS speak, swallow and reduce salivation (Smith et al., 2017).

(Click title to open drug details in a new window.)Company: Orion PharmaLocation: FinlandWebsite:https://www.orion.fi/en/rd/orion-rd/pipeline/Drug Type: Small MoleculeConditions: ALSMechanism Type: Improving muscle functionMechanism: ODM-109 aims in part, to improve breathing in ALS by improving the performance of muscles in the diaphragm. The drug candidate, also known as oral levosimendan, increases the force of contraction of certain muscles by boosting the calcium sensitivity of troponin C.U.S. Status for ALS: Phase IIICommercial Information: The drug candidate is an oral formulation of levosimendan. An intravenous formulation of levosimendan, marketed under the name Simdax, is clinically approved in some countries for the treatment of acute heart failure.

(Click title to open drug details in a new window.)Company: Roche PharmaceuticalsLocation: SwitzerlandWebsite:http://www.roche.comDrug Type: Small MoleculeConditions: ALS, Spinal Muscular AtrophyMechanism Type: Mitochondrial protectantMechanism: Olesoxime is a cholesterol-oxime compound that targets and preserves mitochondrial integrity and function under conditions of cellular stress by modulating the mitochondrial permeability transition pore, and as a result promotes the function and survival of neurons and other cell types under disease-relevant stress conditions. The compound improved muscle function and reduced astrogliosis and microglial activation in preclinical studies in SOD1 ALS mouse models, but failed Phase III trials in ALS.U.S. Status for ALS: DiscontinuedCommercial Information: The company Trophos was developing olesoxime for ALS, but it failed to show a statistically significant effect in a Phase III clinical trial in ALS in Europe, so the company discontinued development of the compound for ALS. This asset was aquired by Roche from Trophos in early 2015.R&D Status: A Phase III, double-blind, placebo-controlled clinical trial of olexosime as add-on therapy to riluzole in 512 people with ALS over 18 months conducted in Europe failed to yield a clinically significant improvement in the 18 month survival rate (Lenglet et al., 2014). The company has shifted it focus for this drug to spinal muscular atrophy (SMA) and a Phase II clinical trial to evaluate long term safety, tolerability and effectiveness of olesoxime is ongoing. Trophos was granted orphan drug designation for olesoxime by the US FDA.

(Click title to open drug details in a new window.)Company: GlaxoSmithKline, GSKLocation: United KingdomWebsite:http://www.gsk.comDrug Type: Protein BiologicConditions: ALSMechanism Type: Axon regenerationMechanism: Ozanezumab (GSK 1223249) is a neurite outgrowth inhibitor (NOGO-A) monoclonal antibody. The rationale for testing ozanezumab in ALS is supported by evidence that NOGO is overexpressed in skeletal muscle of ALS patients, and inhibiting its expression may promote axonal sprouting of new neurites.U.S. Status for ALS: DiscontinuedR&D Status: A Phase II trial in ALS was completed. Primary endpoints were joint rank analysis of function via ALSFRS, and survival. The results indicated a non-significant difference in the joint rank score in favor of placebo (difference -30, P =.120), and all secondary efficacy endpoints supported this finding.

(Click title to open drug details in a new window.)Company: Mitoconix BioWebsite:http://www.futurx.co.il/portfolio/mitoconix-bio/Drug Type: Protein BiologicConditions: ALSMechanism Type: Mitochondrial protectantMechanism: Restoring mitochondrial dynamics, by blocking the hyperactivation of the fission regulator Drp1, may help protect motor neurons in ALS by reducing oxidative stress and increasing energy levels, including at the nerve terminals.U.S. Status for ALS: PreclinicalCommercial Information: P110 is a peptide antagonist of Drp1, a regulator of mitochondrial fission. The approach aims to protect mitochondria in ALS by reducing excess fragmentation of mitochondria. The strategy was developed in the laboratory of Daria Mochly-Rosen at Stanford University in California.

(Click title to open drug details in a new window.)Company: N/ALocation: CanadaDrug Type: Small MoleculeConditions: ALS, Neuropsychiatric DisordersMechanism Type: NMJ stabilizationMechanism: Pimozide may help stabilize NMJs by blocking calcium channels, which may stimulate neurotransmitter release (Patten et al., 2017). Researchers at the University of Montreal in Canada discovered that drug in a high-throughput screen that aimed to identify potential therapies for ALS by looking for drugs that improved mobility of a zebrafish model of the disease.U.S. Status for ALS: Phase IICommercial Information: According to a small 6 week phase II study, researchers at the University of Calgary found that patients taking pimozide experienced multiple side effects including dizziness, blurred vision, and tremors. Now, researchers at the University of Montreal in Canada are developing derivatives of the drug in hopes to improve the drug's tolerability.R&D Status: Pimozide, marketed under the name Orap, is a FDA-approved generic medication for the treatment of neuropsychiatric conditions including Tourette's syndrome. The drug was originally developed in the 1960s as a treatment for schizophrenia. A phase II clinical trial of pimozide in ALS is ongoing.

(Click title to open drug details in a new window.)Company: Chronos TherapeuticsLocation: United KingdomWebsite:http://www.chronostherapeutics.comDrug Type: Small MoleculeConditions: ALS, Alzheimer's disease, Parkinson's disease, Huntington's diseaseMechanism Type: NeuroprotectionMechanism: RDC5 increases autophagy and protein turnover in cells. The approach also activated other pathways including the repair of DNA damage and the reduction of oxidative stress. Chronos has tested RDC5 in both a C. elegans SOD1 model and in SOD1 and TDP-43 mouse models. RDC5 was protective in the C. elegans model, showing a decreased toxicity and a reduced level of toxic protein aggregates.U.S. Status for ALS: N/AR&D Status: A Phase I clinical trial was completed in healthy volunteers.

(Click title to open drug details in a new window.)Company: Tzounopoulos LabLocation: US-PennsylvaniaWebsite:http://phrc.pitt.edu/people/thanos-tzounopoulosDrug Type: Small MoleculeConditions: TinnitusMechanism Type: Neuronal hyperexcitability - Retigabine derivativeMechanism: RL648_81 is a KCNQ2/3-specific channel activator that aims to reduce neuronal hyperexcitability by enabling neurons to return to the resting state upon firing. The drug, also known as RL-81 is a derivative of the FDA-approved epilepsy drug retigabine.U.S. Status for ALS: N/ACommercial Information: Researchers in the laboratory of Thanos Tzounopoulos at the University of Pittsburgh in Pennsylvania developed RL-81 in hopes to improve the safety and selectivity of retigabine, and thereby reduce its side effects.

(Click title to open drug details in a new window.)Company: Revalesio CorporationLocation: US-WashingtonWebsite:http://www.revalesio.comDrug Type: Oxygenated NanobubblesConditions: ALSMechanism Type: Immunomodulation, NeuroprotectionMechanism: RNS60 is a 0.9% saline solution containing oxygenated nanobubbles that is generated by subjecting normal saline to Taylor-Couette-Poiseuille (TCP) flow under elevated oxygen pressure. RNS60, according to studies of a SOD1 mouse model of ALS, may help promote the survival of neurons by activating the PI3K-Akt pathway. The approach may also help reduce inflammation by multiple mechanisms including: increasing CD4+/FoxP3+ regulatory T cells and stimulating the production of anti-inflammatory cytokines.U.S. Status for ALS: Phase IIR&D Status: RNS60 was well tolerated in three phase I clinical trials, one after intravenous administration and two after inhalation. A Phase II study in ALS is ongoing in Italy. An additional trial site in the US, at Massachusetts General Hospital, is also planned.

(Click title to open drug details in a new window.)Company: GileadWebsite:http://www.gilead.comDrug Type: Small MoleculeConditions: ALS, Chronic Angina (Chest Pain)Mechanism Type: Neuronal hyperexcitabilityMechanism: Ranolazine is a sodium channel blocker that may reduce neuronal hyperexcitability by reducing sodium ion influx (the persistent sodium current).U.S. Status for ALS: Phase IIR&D Status: A phase II study is currently recruiting. The study aims to determine whether ranolazine is safe for people with ALS, and reduces muscle cramps and/or twitching in the disease.

(Click title to open drug details in a new window.)Company: Teva PharmaceuticalsWebsite:http://www.tevapharm.com/our_products/Drug Type: Small MoleculeConditions: ALS, Parkinson's DiseaseMechanism Type: Mitochondrial ProtectantMechanism: Rasagiline is an inhibitor of type B monoamine oxidase (MAO-B). It is thought to help protect neurons by bolstering mitochondria by suppressing Ca(2+) efflux through the mitochondrial permeability transition pore (Wu et al., 2015).U.S. Status for ALS: Phase IICommercial Information: The drug is currently used to help treat early stages of Parkinson's disease.R&D Status: Rasagiline did not provide significant benefit in ALS according to the results of two phase II clinical trials.

(Click title to open drug details in a new window.)Company: CytokineticsLocation: US-CaliforniaWebsite:https://www.fortitude-als.com/Drug Type: Small MoleculeConditions: ALS, SMA, and othersMechanism Type: Improving muscle functionMechanism: CK-107, is a fast skeletal muscle troponin activator (FSTA), that aims to increase muscle strength and decrease muscle fatigue in part, by slowing the release of calcium bound to the muscle protein, troponin, increasing the force of muscle contraction.U.S. Status for ALS: Phase IICommercial Information: Cytokinetics is collaborating with Astellas Pharma to develop this potential therapy. The approach, which is structurally distinct from tirasemtiv, is unable to cross the blood-brain-barrier, opening up the possibility that the drug candidate may have a fewer side effects.

(Click title to open drug details in a new window.)Company: GlaxoSmithKline, GSKDrug Type: Small MoleculeConditions: ALS, EpilepsyMechanism Type: Neuronal hyperexcitabilityMechanism: Retigabine is a Kv7 potassium channel activator that may reduce neuronal hyperexcitability by helping neurons return to the resting state upon firing.U.S. Status for ALS: Phase IICommercial Information: The drug is no longer commercially available after June 30, 2017.R&D Status: The phase 2 clinical trial of retigabine in ALS is ongoing. The study aims to determine the safety and tolerability of retigabine in people with ALS. The study also plans to determine whether retigabine reduces motor neuron hyperexcitability in people with the disease.

(Click title to open drug details in a new window.)Company: NeuroNovaLocation: SwedenWebsite:http://www.neuronova.comDrug Type: Protein BiologicConditions: ALSMechanism Type: NeuroprotectionMechanism: sNN0029 is a formulation of vascular endothelial growth factor (VEGF) protein that is suitable for administration into the central nervous system. The drug will be delivered via intracerebroventricular infusion. Multiple studies have shown that VEGF expression is impaired in ALS, and that VEGF treatment ameliorates disease in ALS mouse models.U.S. Status for ALS: DiscontinuedCommercial Information: Neuronova was acquired by Newron Pharmaceuticals in 2012.R&D Status: The company announced initiation of a Phase II study in ALS, but the studies have been terminated, due to issues with development and supples of the infusion system and lack of favorable benefit risk ratio based on review of interim data.

(Click title to open drug details in a new window.)Company: RhinoCyteLocation: US-KentuckyWebsite:http://www.rhinocyte.com/Drug Type: Stem Cell TherapyConditions: ALS, Parkinson's disease, multiple sclerosis, spinal cord injury.Mechanism Type: NeuroprotectionMechanism: RhinoCyte develops therapies based on autologous adult olfactory-derived neural progenitor stem cells (RhinoCytes). It is unclear whether this program is active.U.S. Status for ALS: PreclinicalCommercial Information: The company was founded in partnership with MetaCyte Business Lab, LLC.R&D Status: Preclinical. RhinoCyte Cells were granted Orphan Drug Designation for use in treatment of ALS in 2009.

(Click title to open drug details in a new window.)Company: Covis PharmaLocation: Switzerland, US-North CarolinaWebsite:http://www.covispharma.com.Drug Type: Small moleculeConditions: ALS, Alzheimer's disease, Parkinson's disease, Huntington's disease, Spinocerebellar Ataxia Type 2, Spinal Cord InjuryMechanism Type: Glutamate Excitotoxicity BlockerMechanism: Riluzole is a benzothiazole. Its mechanism of action is unknown, but its pharmacological properties include inhibition of glutamate release, inactivation of voltage-dependent sodium channels, modulation of signaling pathways activated by neurotransmitter binding to excitatory amino acid receptors (EAAT2).U.S. Status for ALS: FDA ApprovedCommercial Information: Covis Pharma Sarl acquired the commercial rights to Rilutek from Sanofi-aventis in the U.S. in 2013.R&D Status: Riluzole is the first FDA approved disease-modifying therapy for ALS. The effect on survival is moderate, and the drug prolongs survival by an estimated 2-6 months. It is currently being evaluated as a treatment for Alzheimer's disease, Spinocerebellar ataxia, spinal cord injury and other conditions. Riluzole is no longer being pursued as a potential therapy for Parkinson's and Huntington's diseases due to a lack of effect observed in clinical studies.

(Click title to open drug details in a new window.)Company: Sangamo BiosciencesLocation: US-CaliforniaWebsite:http://www.sangamo.comDrug Type: Gene TherapyConditions: ALSMechanism Type: NeuroprotectionMechanism: SB-509 is an injectable formulation of a plasmid encoding a zinc finger DNA-binding protein transcription factor designed to upregulate the expression of the gene encoding vascular endothelial growth factor (VEGF-A).U.S. Status for ALS: DiscontinuedCommercial Information: Sangamo acquired Ceregene in 2013.R&D Status: In 2010, Sangamo Biosciences completed a Phase II clinical trial to evaluate their drug, SB-509, in subjects with ALS. The company does not appear to have plans for further developing this drug for ALS.

(Click title to open drug details in a new window.)Company: SciFluorLocation: US-MassachusettsWebsite:http://scifluor.com/our-approach/our-approach-fluoro.phpDrug Type: Small MoleculeConditions: ALS, Epilepsy, TinnitusMechanism Type: Neuronal hyperexcitability - Retigabine derivativeMechanism: SF0034 is a KCNQ2/3-specific channel activator that aims to reduce neuronal hyperexcitability by enabling neurons to return to the resting state upon firing. The drug is a fluorinated-derivative of the FDA-approved epilepsy drug retigabine. U.S. Status for ALS: PreclinicalCommercial Information: Researchers in the laboratory of Thanos Tzounopoulos at the University of Pittsburgh in Pennsylvania developed SF0034 in hopes to improve the safety and selectivity of retigabine, and thereby reduce its side effects.

(Click title to open drug details in a new window.)Company: Opko HealthLocation: USA-FloridaWebsite:http://www.opko.comDrug Type: Small MoleculeConditions: Parkinson's diseaseMechanism Type: NeuroprotectionMechanism: SR3306 is an orally bioavailable, aminopyrimidine inhibitor of c-Jun N-terminal kinases (JNKs), a class of mitogen-activated protein kinases (MAPK) that respond to conditions of stress and regulate neuronal survival. The compound is orally available and CNS penetrant according to studies in animal models, as well as protects neurons in two animal models of Parkinson's disease. The mechanism of action is potentially relevant to ALS due to a evidence for link between JNK activation and TDP-43 toxicity.U.S. Status for ALS: N/ACommercial Information: Opko is developing SR3306 under an exclusive license from the Scripps Research Institute, and preclinical testing is being conducted in Philip LoGrasso's laboratory at the Scripps Research Institute in Jupiter, FL.R&D Status: N/A

(Click title to open drug details in a new window.)Company: Daiichi Sanyo, IncLocation: US-New JerseyWebsite:http://www.dsi.com/homeDrug Type: Protein BiologicConditions: ALSMechanism Type: Promoting appetite (Cachexia)Mechanism: SUN11031 is a peptide hormone that is a ghrelin receptor agonist (it is a synthetic form of ghrelin). In preclinical studies in the SOD1 models of ALS, ghrelin attenuated disease progression through orexigenic effects (promoting appetite), as well as by preventing muscle wasting and weight loss via non-oregigenic effects.U.S. Status for ALS: InactiveCommercial Information: In 2015, Asubio Pharmaceuticals merged with Daiichi Sanyo's US subsidiary. Previously, in 2013, Asubio Pharmaceuticals presented preclinical studies on the beneficial effects of ghrelin receptor agonist in ALS mouse models. The program appears to have been discontinued.R&D Status: A Phase II study in Cachexia Associated With Chronic Obstructive Pulmonary Disease (COPD) was completed.

(Click title to open drug details in a new window.)Company: EvotecLocation: GermanyWebsite:http://www.evotec.comDrug Type: Small MoleculeConditions: ALS, Alzheimer's diseaseMechanism Type: AnitoxidantMechanism: EV302 is an inhibitor of monoamine oxidase B, an enzyme that breaks down dopamine, and contributes to production of free radicals and oxidative stress conditions.U.S. Status for ALS: PreclinicalCommercial Information: The compound was originally licensed to Evotec by Roche in 2006, but in 2011, the two companies entered into an exclusive license agreement to co-develop it for Alzheimer's disease (AD). In July 2015, the companies announced that a Phase IIb trial in AD had failed. Evotec established a collaboration with the Harvard Stem Cell Institute scientists Dr. Kevin Eggan and Dr. Lee Rubin in 2013 to identify drugs that slow motor neuron degeneration in ALS, in a program called CureMN.R&D Status: The company announced in 2015 that the drug failed in a Phase IIb clinical trial in Alzheimer's disease.

(Click title to open drug details in a new window.)Company: ImStar TherapeuticsLocation: CanadaWebsite:http://www.imstartx.com/Drug Type: Protein BiologicConditions: ALSMechanism Type: ImmunomodulationMechanism: TDP-43 abnormally accumulates aggregates in the cytoplasm of the vast majority of ALS patients. In addition, recent studies have shown that TDP-43 activates NFkB, and may increase inflammation via this pathway. This approach, known as TDP-43-associated nuclear factor-kB (NFkB) activation (TANA) inhibitors, aims to reduce neuroinflammation by targeting this pathway.U.S. Status for ALS: PreclinicalCommercial Information: The company was co-founded by Dr. Jean-Pierre Julien from Laval University. The last update from the company was in January 2014.R&D Status: Preclinical

(Click title to open drug details in a new window.)Company: ALS Therapy Development InstituteLocation: US-MassachusettsWebsite:http://www.als.netDrug Type: Protein BiologicConditions: ALSMechanism Type: ImmunomodulationMechanism: TDI-846 (blocking antibody to CD40L) is designed to modulate the immune response associated with disease progression in ALS.U.S. Status for ALS: PreclinicalCommercial Information: ALSTDI has licensed its CD40L antibody program to Anelixis Therapeutics. ALSTDI is collaborating with Biogen and UCB Pharma on development of a newer version of the anti-CD40L antibody called CDP7657. For full details of the ALS TDI pipeline click here: http://www.alstdi.org/als-research/.R&D Status: Preclinical

(Click title to open drug details in a new window.)Company: TreewayLocation: NetherlandsWebsite:http://www.treeway.nl/Drug Type: Small MoleculeConditions: ALSMechanism Type: AnitoxidantMechanism: TW001 is an oral formulation of the free radical scavenger edaravone. Edaravone, marketed under the name Radicut and Radicava, is approved for the treatment of ALS in Japan and South Korea. But this therapy requires frequent intravenous infusions. TW001 is being developed in hopes to provide an option for people with ALS that is easier and more convenient to administer.U.S. Status for ALS: Phase IR&D Status: TW001 was granted orphan drug designation by the FDA and the EMA. In two Phase I studies of TW001 in healthy volunteers and ALS patients, the drugs was safe and well tolerated. A Phase II/III study is planned.

(Click title to open drug details in a new window.)Company: TreewayLocation: NetherlandsWebsite:http://www.treeway.nl/Drug Type: Gene TherapyConditions: ALSMechanism Type: NeuroprotectionMechanism: TW002 is a gene therapy for ALS, which uses AAV5 vectors to administer glial cell line-derived neurotrophic factor (GDNF) in order to provide neurotrophic support for motor neurons.U.S. Status for ALS: PreclinicalCommercial Information: Treeway obtained exclusive rights from uniQure to develop AAV5-GDNF for ALS. Treeway is collaborating with the team of Prof. Clive Svendsen, PhD, director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute in Los Angeles, CA to advance the development of TW002 for ALS.R&D Status: Preclinical

(Click title to open drug details in a new window.)Company: TreewayLocation: NetherlandsWebsite:http://www.treeway.nl/Drug Type: Gene TherapyConditions: ALSMechanism Type: ImmunomodulationMechanism: TW003 is a vaccine therapy to restore immune balance by targeting the adaptive immune response in ALS. The drug incorporates a patented viral gene delivery platform called SVac. SVac is reported as a safe, highly efficient and nonimmunogenic vector platform.U.S. Status for ALS: PreclinicalCommercial Information: The project is being conducted in collaboration with Amarna Therapeutics.R&D Status: Preclinical

(Click title to open drug details in a new window.)Company: Teva Pharmaceutical IndustriesLocation: IsraelWebsite:http://www.tevapharm.comDrug Type: Small MoleculeConditions: ALSMechanism Type: Glutamate Excitotoxicity BlockerMechanism: Talampanel is a selective non-competitive antagonist of AMPA receptors, a type of glutamate receptor. Talampanel was tested as a drug to reduce neuronal death due to glutamate excitotoxicity.U.S. Status for ALS: DiscontinuedR&D Status: A Phase II trial in ALS was completed in 2010, but no efficacy measure reached statistical significance in treated vs. control patients, at two different doses tested. The program was discontinued.

(Click title to open drug details in a new window.)Company: CytokineticsLocation: US-CaliforniaWebsite:http://www.cytokinetics.comDrug Type: Small MoleculeConditions: ALSMechanism Type: Improving muscle functionMechanism: Tirasemtiv is a fast skeletal muscle troponin activator (FSTA) that increases the force of contraction by boosting the sensitivity of troponin to calcium.U.S. Status for ALS: DiscontinuedCommercial Information: Intolerability of tirasemtiv experienced by many people with ALS may have interfered with the analysis. Cytokinetics, in partnership with Astellas Pharma, is now testing a new FSTA, CK-107, which is unable to cross the blood brain barrier, in hopes to improve tolerability of this approach.R&D Status: A Phase IIb clinical trial in ALS in 2014 found mixed results: no statistically significant difference was detected between ALSFRS-R scores between treated and untreated groups, however, a statistically significant improvement in Slow Vital Capacity (SVC) in treated patients was observed. These findings led to the initiation of a Phase III trial, which found that drug provided no benefit, resulting in the drug to be discontinued.

(Click title to open drug details in a new window.)Company: ProteostasisLocation: US-MassachusettsWebsite:http://www.proteostasis.com/Drug Type: Small MoleculeConditions: Alzheimer's disease, Parkinson's diseaseMechanism Type: Protein aggregate clearanceMechanism: In collaboration with Biogen, the company developed novel inhibitors of Usp14, a deubiquitinating enzyme, to enhance clearance of aggregation-prone proteins such as alpha synuclein and tau. Inhibition of Usp14 promotes clearance of TDP-43 by retaining ubiquiting chains, suggesting this could be a promising therapeutic approach in ALS. However, Amgen recently reported that the company could not reproduce these published results. The status of this approach is unknown.U.S. Status for ALS: N/ACommercial Information: Proteostasis Therapeutics developed inhibitors of Usp14 in partnership with Biogen with technology licensed from Harvard University. This partnership ended in December 2016. The Usp14 technology was originally developed at Harvard Medical School by Professors Daniel Finley, Ph.D., and Randall King, Ph.D., M.D. R&D Status: Preclinical

(Click title to open drug details in a new window.)Company: Voyager TherapeuticsLocation: Cambridge, MAWebsite:http://voyagertherapeutics.com/programs.phpDrug Type: Gene TherapyConditions: SOD1 ALSMechanism Type: SOD1-Lowering TherapyMechanism: VY-SOD101 is an adeno-associated viral (AAV)-based gene therapy that aims to slow progression of SOD1 ALS by reducing levels of ALS-linked mutant SOD1. SOD1 mutations account for approximately 20% of familial forms of ALS.U.S. Status for ALS: PreclinicalCommercial Information: REGENXBIO licensed their Next Generation AAV (NAV) technology to Voyager Therapeutics for ALS and other rare indications. The gene therapy approach was originally developed in the laboratory of Professor James Wilson, M.D., Ph.D. at the University of Pennsylvania Perelman School of Medicine in Philadelphia, PA.R&D Status: Voyager Therapeutics is targeting an IND filing for VY-SOD101 in late 2017.

(Click title to open drug details in a new window.)Company: XonovoLocation: IsraelWebsite:http://www.futurx.co.il/Drug Type: Small MoleculeConditions: ALS, Alzheimer's disease, Batten's diseaseMechanism Type: NeuroprotectionMechanism: XN-001 is a small molecule synthetic derivative of the natural brain metabolite Lanthionine Ketimine (LK). It targets collapsin response mediator protein (CRMP2). XN-001 has shown promising results in mouse models of Alzheimer's disease and ALS.U.S. Status for ALS: PreclinicalCommercial Information: The technology was licensed from Oklahoma Medical Research Foundation. XoNovo Ltd. was founded by Dr. Rafi Gidron, the founder and chairman of Israel Brain Technologies and by Professor Kenneth Hensley from Toledo University in Ohio. The company is based on Hensley's work on lanthionine ketimine.R&D Status: Preclinical